Striatal dopamine during sensorial stimulations: a [18F]FDOPA PET study in human and cats.

Sensory stimulations of the forelimb in cats are known to increase dopamine release in the ipsilateral striatum and to decrease it in the homologous contralateral structure. Using positron emission tomography in both humans and cats, the present study shows that such sensory stimulations greatly reduce [(18)F]FDOPA accumulation ipsilateral to the stimulation (by 40.4% and 26.4% in the human caudate and putamen, respectively, and by 33.3% in the cat striatum). This decrease in striatal [(18)F]FDOPA uptake suggests a reduced DA storage resulting from the increased amine release. No change was observed in the contralateral striatum in neither human or cat suggesting, in contrast, that [(18)F]FDOPA accumulation is not facilitated by decreased DA release. These results support the hypothesis that sensory stimulations activate a non-synaptic mode of dopamine release.

PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow.

Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [(11)C]raclopride (BP(raclo)), a radioligand with good specificity for dopamine (DA) receptors of the D(2) type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg(-1) h(-1); i.m.) and anaesthetised with halothane (1.5%). Non-specific binding was evaluated in the cerebellum. In the striatum of both sides, the BP(raclo) was unmodified by ketamine anaesthesia when compared with awake animals. In contrast, a large increase in BP(raclo) was observed under halothane anaesthesia. The non-specific binding of [(11)C]raclopride, evaluated in the cerebellum, was also unchanged under ketamine anaesthesia but greatly increased under halothane anaesthesia. To evaluate whether changes in the cerebral blood flow (CBF) resulting from the different experimental situations could be at the root of these discrepancies, injections of [(15)O]H(2)O were performed; measurements revealed a drastically increased CBF under halothane anaesthesia and a slight enhancement under ketamine anaesthesia, when compared with the waking state. These results are the first to be obtained on this topic in awake cats, and show that the BP(raclo) is greatly dependent on alterations in the CBF.

Effects of amphetamine and evoked dopamine release on [11C]raclopride binding in anesthetized cats.

The effects of halothane and ketamine anesthesia on [11C]raclopride binding were assessed in the cat striatum at basal conditions and after drug- or depolarization-induced dopamine (DA) release using Positron Emission Tomography. At baseline, Scatchard analyses revealed that the higher [11C]raclopride binding found under halothane anesthesia was mainly attributable to a higher radioligand apparent affinity. Decreased [11C]raclopride binding was demonstrated following amphetamine under ketamine but not under halothane anesthesia. Under ketamine anesthesia transient DA overflows induced by direct stimulations of DA neurons through an intracerebral electrode induced transient changes in [11C]raclopride binding with a remarkable spatiotemporal accuracy. No effect was observed under halothane anesthesia. The failure to detect competition between DA and [11C]raclopride for binding on D(2)-receptors under halothane anesthesia might reflect, as already reported for other brain receptor systems, a halothane-promoted conversion of D(2)-receptors to a state of lower affinity for DA. It is suggested that the affinity state of receptors is a factor to be considered in in vivo ligand-activation studies.